Small-cell lung cancer (SCLC) is expected to account for 25% of the approximate 170,000 cases of lung cancer diagnosed in the United States in 2002. Although sensitive and responsive to chemotherapy, SCLC has an increased propensity for early metastases, with relapses being common and long-term survival rates being poor. Clinical trials have played a vital role in expanding our knowledge base for this disease and have resulted in newer modalities, including chemotherapeutic agents, prophylactic cranial irradiation, and thoracic radiotherapy designed to improve overall outcomes. Clinical trials have also served to clarify the role of surgery in a disease that traditionally has been thought to be nonoperable. This review will focus on the results of clinical trials that have had an effect on the treatments of patients with limited and extensive-stage SCLC, with recommendations from the National Comprehensive Cancer Network being emphasized.